The development and use of cancer vaccines either as a monotherapy or in combination with other therapeutic modalities represents an important new strategy for the therapy of many cancers. There is no standard treatment for patient with non-metastatic androgen-independent prostate cancer (AIPC) (D0.5). We previously performed the first randomized study in this patient population involving vaccine and hormone (nilutamide) combination therapy. To our knowledge this report is the first prospective analysis of overall survival data in patients with stage D0.5 AIPC. The initial study randomized 21 patients to treatment with nilutamide and 21 patients to treatment with a PSA poxvirus-based vaccine. The vaccine was an admixture containing a vaccinia vector with the gene for PSA combined with vaccinia containing the costimulatory molecule B7.1. As part of this vaccine strategy, patients also received monthly boosts of fowlpox-PSA with GM-CSF and IL-2 with all vaccinations. Patients who developed rising serum PSA levels on either arm could cross-over to receive both vaccine and nilutamide. Initial data demonstrated a clinical benefit in patients treated with combination vaccine and nilutamide. Patients' characteristics were reviewed and overall survival was determined using the social security death index. Actuarial analyses of the data using the Kaplan-Meier method were performed. The overall survival from on-study date in all randomized patients was 4.6 years with 3-year overall survival = 71% and 5-year overall survival = 48%. There was no difference in overall survival in all patients based on Gleason Score (GS) or PSA at diagnosis, orchiectomy, radical prostatectomy, or radiation therapy. However, a subgroup analysis showed a trend to improved overall survival for patients treated with vaccine alone or vaccine then nilutamide (compared to nilutamide alone or nilutamide then vaccine). These studies demonstrate that prostate cancer vaccines can be safely used with hormone therapy and that the combination of using vaccine followed by hormone has a potential advantage over the reciprocal scheduling regimen. These studies have thus formed the basis for further clinical trials in patients with early state prostate cancer. Metastatic prostate cancer is a disease stage for which very few therapeutic options are available that provide long-lasting anti-cancer effects. Vaccine-mediated immunotherapy offers a potential safe and effective therapeutic modality. The NCI has developed viral-based vaccines that contain the tumor-associated antigen PSA and three human T-cell costimulatory molecules, designated TRICOM. The purpose of this clinical trial was to determine the safety of this vaccine regimen and its ability to generate immune responses and to indicate any evidence of patient benefit in patients with metastatic prostate cancer. The 15 patients enrolled in this study had metastatic prostate cancer. Patients were given either rF-PSA/TRICOM alone, or rV-PSA/TRICOM followed by rF-PSA/TRICOM on a prime-and-boost schedule, with or without r-GM-CSF protein or rF-GM-CSF vector. PSA-specific immune responses were measured using an ELISPOT assay for IFN-gamma production. Some grade 2 toxicities were seen in patients who received a higher dose of rFGM-CSF, but no toxicities exceeded grade 2. PSA-specific immune responses were seen in 4 of 6 patients analyzed and, most importantly, decreases in serum PSA velocity were observed in 9 of 15 patients. Based on the safety and preliminary immunogenicity and patient benefit results of this trial, it is recommended that a randomized phase II study employing this vaccine be initiated in patients with less advanced prostate cancer. Other accomplishments are described in the following publications: Schlom J, Arlen P, Gulley J. Cancer vaccines: moving beyond current paradigms. Clin Cancer Res. 3776-82, 2007. [Journal] Arlen P, Madan R, Hodge J, Schlom J, Gulley J. Combining vaccines with conventional therapies for cancer. Update on Cancer Therapeutics. 2: 33-9, 2007. [Journal] Arlen P, Skarupa L, Pazdur M, Seetharam M, Tsang K, Grosenbach D, Feldman J, Poole D, Litzinger M, Steinberg S, Jones E, Chen C, Marte J, Parnes H, Wright J, Dahut W, Schlom J, Gulley J. Clinical safety of a viral vector-based prostate cancer vaccine strategy. J Urol. 2007. In Press. [Journal] Arlen P, Gulley J, Madan R, Hodge J, Schlom J. Preclinical and clinical studies of recombinant poxvirus vaccines for carcinoma therapy. Crit Rev Immunol (Supp). 2007. In Press. [Journal] Gulley J, Madan R, Arlen P. Enhancing efficacy of therapeutic vaccinations by combination with other modalities. Vaccine. 2007. In Press. [Journal] Madan R, Lieberman R, Gulley J, Dahut W, Arlen P. A significant PSA response to low dose ketoconazole in a patient with non-metastatic androgen independent prostate cancer (AIPC) and a review of the literature. Amer J Therapeutics. 14: 310-3, 2007. [Journal] Madan RA, Arlen PM, Gulley JL. PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma. Expert Opin Biol Ther. 7: 543-54, 2007. [Journal] Hodge JW, Greiner JW, Tsang KY, Sabzevari H, Kudo-Saito C, Grosenbach DW, Gulley JL, Arlen PM, Marshall JL, Panicali D, Schlom J. Costimulatory molecules as adjuvants for immunotherapy. Front. Biosci. 11: 788-803, 2006. [Journal] Arlen PM, Dahut WL, Gulley JL. Immunotherapy for prostate cancer: what's the future?. Hematol. Oncol. Clin. North Am. 20: 965-83, 2006. [Journal] Lattouf JB, Arlen PM, Pinto PA, Gulley JL. A phase I feasibility study of an intraprostatic prostate-specific antigen-based vaccine in patients with prostate cancer with local failure after radiation therapy or clinical progression on androgen-deprivation therapy in the absence of local definitive therapy. Clinical genitourinary cancer. 5: 89-92, 2006. [Journal] Arlen PM, Pazdur M, Skarupa L, Rauckhorst M, Gulley JL. A randomized phase II study of docetaxel alone or in combination with PANVAC-V (vaccinia) and PANVAC-F (fowlpox) in patients with metastatic breast cancer (NCI 05-C-0229). Clin. Breast Cancer. 7: 176-9, 2006. [Journal] Ahlers CM, Camphausen K, Citrin D, Arlen PM, Gulley JL. A pilot trial of a carcinoembryonic antigen/ TRICOM-based vaccine and radiation to liver metastases in patients with carcinoembryonic antigen-positive solid tumors. Clinical colorectal cancer. 6: 72-5, 2006. [Journal] Tarassoff CP, Arlen PM, Gulley JL. Therapeutic vaccines for prostate cancer. Oncologist. 11: 451-62, 2006. [Journal] Madan RA, Gulley JL, Arlen PM. PSA-based vaccines for the treatment of prostate cancer. Expert review of vaccines. 5: 199-209, 2006. [Journal] Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J, Steinberg SM, Jones E, Chen C, Marte J, Schlom J, Dahut W. A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin. Cancer Res. 12: 1260-9, 2006. [Journal] Garnett CT, Greiner JW, Tsang KY, Kudo-Saito C, Grosenbach DW, Chakraborty M, Gulley JL, Arlen PM, Schlom J, Hodge JW. TRICOM vector based cancer vaccines. Curr. Pharm. Des. 12: 351-61, 2006. [Journal] Madan RA, Arlen PM. Abiraterone. Cougar Biotechnology. IDrugs : the investigational drugs journal. 9: 49-55, 2006. [Journal] Dahut WL, Lakhani NJ, Gulley JL, Arlen PM, Kohn EC [summary truncated at 7800 characters]